New Insights Into Link Between Kidney Stones, Urinary Tract Infection

Kidney stone disease (KSD) and urinary tract infection (UTI) often coexist, and stone removal may reduce the risk of recurrent UTI, authors of a systematic review concluded.

The review showed a bidirectional nature of the relationship between KSD and UTI, as stone formers had a high prevalence of UTI and patients evaluated for UTI had a high prevalence of KSD. A recent retrospective review of 819 stone formers and 2,477 individuals with no history of KSD showed a six- to seven-fold greater risk of UTI, including patients with calcium oxalate stones or urate stones.

Several other studies included in the review showed that stone removal was associated with lower rates of UTI, including substantial reductions in the rate of recurrent UTI in patients with a history of infection, reported Bhaskar K. Somani, MD, of University Hospital Southampton in England, and co-authors in Current Urology Reports.

“Our SR [systematic review] clearly shows that UTI and KSD are mutually coexisting, and reciprocally causal, and such patients should be counseled for proactive intervention by stone removal, especially when UTIs are recurrent or additional risk factors are present, irrespective of stone composition,” the authors wrote. “To prevent further UTI episodes, if possible, a stone culture must be obtained for an effectively targeted antibiotic treatment regimen tailored to bacterial prevalence.”

Evidence of an association between chronic/recurrent UTI and stone formation dates back more than 30 years. A study involving 43 patients with bacteriuria and renal stones distinguished between those with stone-related infection and bacteriuria versus those with UTI and no KSD. The authors of that early report concluded that “active stone intervention aimed at eradicating the infection can absolve risk of permanent UTI.”

The nature of the association remained unclear, Somani and co-authors noted. However, the observed increased risk of urinary infection in patients with KSD created an “imperative to establish if UTI is the primary driving force in stone formation or does bacterial colonization on stones increase the risk of severe sepsis.” Additionally, no consensus exists about the optimal treatment for patients with kidney stones that might contribute to UTI.

The authors performed a systematic review to explore the relationship between KSD and UTI and to “decrypt evidence for hypothesis which favors that treatment of KSD can provide a resolution to recurrent UTI in this cohort.” They also wanted to identify current hypothesized mechanisms of bacterial impact on stone formation and growth.

Beginning with 1,900 publications, the authors whittled the list down to 17 articles. Multiple studies published over the past 10 to 20 years established the association between KSD and UTI. Others provided insights into the nature of the association.

A study of 1,325 adults with KSD followed for 7 years showed a 28% incidence of positive urine cultures, substantially higher than the rate observed in the general population. Investigators further found that UTI occurred most frequently in association with Proteus infections and in patients with magnesium ammonium phosphate stones. Oxalate-containing calculi predominated in patients without infection, Somani and co-authors said.

In a study of 100 patients with urinary symptoms, 79% had infections, caused predominantly by E. coli (30%), Proteus (19%), and Klebsiella (11%). Almost 20% of patients with infection had KSD.

Just last year, a comparison of stone formers and non-stone formers with a median follow-up of 19 years showed an infection rate of 18.7% among stone formers versus 14.1% in the control group. Among 155 stone formers who developed a UTI, 63 had at least one stone recurrence, which Somani and colleagues interpreted as evidence of “the tight link between these conditions.”

The difference translated into a UTI hazard of 5.73 for the stone formers versus non-formers (P<0.001). An increased risk of UTI was evident for patients with calcium oxalate stones (HR 6.36, 95% CI 4.82-8.40) and for those with urate stones (HR 6.87, 95% CI 2.82-16.72) versus other stone compositions.

A prospective study of 100 patients undergoing elective stone removal showed a UTI prevalence of 36%. The most common bacterial species in urine samples were E. coli, Enterococcus species, and Klebsiella/Enterobacter species, whereas E. coli, P. mirabilis, and Klebsiella species were most commonly found in stone matrices. The study also showed that recurrent UTI was associated with “almost all kidney stone compositions.”

The review included several studies that investigated the hypothesis that surgical intervention for stones might reduce bacterial burden, recurrent UTI, and bacteriuria. A cohort study involving 103 patients with a history of recurrent UTI and KSD showed that stone clearance led to resolution of UTI. As the stone-free rate declined during 12 months of follow-up, so did the infection-free rate (P<0.001). Moreover, eight of 10 patients with stone recurrence also had a UTI recurrence.

On the other hand, a retrospective analysis of 120 patients with recurrent UTI and KSD showed that 52% of patients developed recurrent infection after stone removal. Infection with E. coli was associated with successful clearance of infection, whereas Enterococcus was associated with failed clearance. The observation suggested that the antibiotics given before or after stone removal might alter the effect of the surgical procedure on recurrent UTI, Somani and co-authors noted.

“Future work should focus on enhanced techniques of bacterial cultures and should analyze the primitive molecular mechanism underlying the crystallization of organic and inorganic components in urine in order to finally solve the ‘chicken and egg’ dilemma,” the authors said in their summary. “Perhaps, a real cost and quality of life analysis of treatment versus surveillance in these patients should also be considered.”